P1185: A PROSPECTIVE SINGLE-CENTER PHASE 2 STUDY OF ZANUBRUTINIB PLUS R-CHOP IN TREAT-NAÏVE INTRAVASCULAR LARGE B CELL LYMPHOMA
Authors: Yan Zhang, Chao Chen, Danqing Zhao, Zhe Zhuang, Chong Wei, Wei Wang, Wei Zhang, Dao-Bin Zhou
Journal: HemaSphere (2023)

Topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical Background: Intravascular large B-cell lymphoma (IVLBCL) is a rare disease for which there is no available standard treatment. Zanubrutinib is a selective Bruton Tyrosine kinase(BTK) inhibitor and has shown activity in several B cell lymphomas. Aims: We aimed to ascertain the safety and activity of zanubrutinib plus R-CHOP (rituximab, cyclophosphamide, epirubicin, vindesine, and prednisolone) for patients with previously untreated IVLBCL Methods: This is a prospective, single-arm, phase 2 trial at Peking Union Medical College Hospital in China. Eligible patients had untreated histologically confirmed IVLBCL, were aged>18 years, had adequate bone marrow and organ function, had no active infections or bleeding. Patients received 8 cycles of zanubrutinib (160mg bid orally) plus R-CHOP (rituximab 375 mg/m² intravenously on day 1; cyclophosphamide 750 mg/m², epirubicin 70 mg/m², and vindesine 4mg intravenously on day 1 and prednisolone 100 mg orally on days 1–5) every 3 weeks. The primary endpoint was 2-year progression-free survival. Secondary end points included safety profile. The trial is registered at ClinicalTrials.gov (NCT 04899570) and is still recruiting. Results: By 14th February,2023, 23 patients were enrolled into the study, 13 patients had finished 8 cycles treatment, 9 were still under treatment and 1 withdrew due to adverse events. All 23 patients were Ann Arbor IVB stage (median age 59, 14 males), and in intermediate-high/high risk group (IPI 3-5). 13 patients had the end of treatment evaluation and 19 had the interim of treatment evaluation. All of them were in the efficacy population. 18 patients achieved complete remission and 1 achieved partial remission in the interim of treatment evaluation. 12 patients achieved complete remission and 1 achieved partial remission in the end of treatment evaluation. The overall response rate was 100% in the interim and end of treatment evaluation. 14 patients who had central nerves system involvement all got significant improvement in symptoms and MRI scans. Median follow-up of patients who completed 8 cycles of treatment was 439 days (range 266-693), no relapsing occurred and 1 patient died of septic shock 3 months after the completion of treatment. Every patient was enrolled into the safety population. The most common adverse effect (AE) were hematological toxicities, including Grade 3-4 neutropenia (15/23), Grade 3 anemia (5/23) and Grade 3-4 thrombocytopenia (5/23); all the hematological AE were mainly occurred in the first cycle. Any grade non-hematological toxicities included: fatigue(13/23),infection(10/23),infusion action(11/23),anorexia(13/23), vomiting(12/23),hypertention(3/23). There was no dose modification due to AE.Summary/Conclusion: Zanubrutinib plus R-CHOP demonstrated promising efficacy as a front-line regimen in IVLBCL, even in the CNS involvement patients. This regimen is well tolerated and it warrants future investigation in larger-scale population and long-term follow-up. Funding: National High Level Hospital Clinical Research Funding,2022-PUMCH-A-192 *Corresponding author Dao-bin Zhou Address: Shuaifuyuan No. 1, Dongcheng District, Beijing, China. Email: [email protected] Tel: +86 13901113623 Keywords: Lymphoma therapy, Non-Hodgkin's lymphoma, B cell lymphoma